This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Epidemics of flavivirus infections continue to be a major public health concern worldwide. More than two billion people are at risk of being infected with members of these viruses, including Japanese encephalitis (JE) virus in Asia and Australia;yellow fever (YF) virus in Africa and Latin America;West Nile (WN) virus in Africa Central Europe and America;tick-borne encephalitis (TBE) complex viruses, including Russian spring summer encephalitis (RSSE) and Central European encephalitis (CEE) viruses in the temporal regions of Europe and Asia;and four serotypes of dengue (DEN-1, -2, -3, and -4) viruses in the tropical and subtropical regions of the world. With the exceptions of YF, JE and TBE, vaccines are not available to prevent other flavivirus infections in humans. The vaccine candidates to be tested have previously been shown in outbred mice model, several avian species and horses to be well-tolerated, and no undesired injection reaction was observed in all ages of vaccinated mice, birds or horses. Serum neutralizing antibodies persisted for more than two years after primary immunization. The objective of this study is to assess the safety, immunogenicity and protective efficacy of novel vaccine candidates against JEV, WNV, YF and DEN 1-4 challenge in nonhuman primates. The results of this study will provide essential data for next study phase with the final goal for supporting human clinical trials.